Socioeconomic status and cardiovascular mortality in over 170,000 cancer survivors.

AIMS: Cardiovascular health is acknowledged as a crucial concern among cancer survivors. Socioeconomic status (SES) is an essential but often neglected risk factor for cardiovascular disease (CVD). We conducted this study to identify the relationship between SES and CVD mortality in cancer survivors. METHODS AND RESULTS: Using the National Health Insurance Service-National Health Examinee database, we identified cancer survivors diagnosed and surviving beyond 5 years post-diagnosis. SES was assessed based on insurance premiums and classified into 5 groups. The primary outcome was overall CVD mortality. This study analyzed 170 555 individuals (mean age 60.7 ± 11.9 years, 57.8% female). A gradual increase in risk was observed across SES groups: adjusted hazard ratios (95% confidence intervals) for overall CVD mortality were 1.15 (1.04-1.26), 1.28 (1.15-1.44), 1.31 (1.18-1.46), and 2.13 (1.30-3.49) for the second, third, and fourth quartile, and medical aid group (the lowest SES group) compared to the highest SES group, respectively (p for trend < 0.001). The lowest SES group with hypertension exhibited a 3.4-fold higher risk of CVD mortality compared to the highest SES group without hypertension. Interaction analyses revealed that low SES synergistically interacts with hypertension, heightening the risk of CVD mortality (synergy index 1.62). CONCLUSION: This study demonstrates a significant correlation between low SES and increased CVD mortality among cancer survivors. Particularly, the lowest SES group, when combined with hypertension, significantly escalates CVD mortality. Our findings underscore the critical importance of recognizing SES as a significant risk factor for CVD mortality in this population of cancer survivors.

Our population-based cohort study, involving over 170 000 cancer survivors, demonstrates a significant association between socioeconomic status (SES) and cardiovascular disease (CVD) mortality.

Antihypertensive Medication Adherence and Cardiovascular Outcomes in Patients With Cancer: A Nationwide Population-Based Cohort Study.

Background Hypertension is an important cause of morbidity, which predisposes patients to major cardiovascular events and mortality. The aim of this study was to explore the association between adherence to antihypertensive medication and clinical outcomes in adult patients with cancer. Methods and Results Using the 2002 to 2013 Korean National Health Insurance Service-National Sample Cohort, we extracted adult patients with cancer treated with antihypertensive medications. Based on the medication possession ratio value, participants were divided into 3 groups: good (medication possession ratio ≥0.8), moderate (0.5≤ medication possession ratio <0.8), and poor (medication possession ratio <0.5) adherence groups. The primary outcomes were overall and cardiovascular mortality. The secondary outcome was cardiovascular events requiring hospitalization due to major cardiovascular diseases. Among 19 246 patients with cancer with concomitant hypertension, 66.4% were in the nonadherence group (26.3% were moderate and 40.0% were poor adherence group). Over a median of 8.4 years of follow-up, 2752 deaths and 6057 cardiovascular events occurred. Compared with the good adherence group, the moderate and poor adherence groups had a 1.85-fold and 2.19-fold increased risk for overall mortality, and 1.72-fold and 1.71-fold elevated risk for cardiovascular mortality, respectively, after adjustment for possible confounders. Furthermore, the moderate and poor adherence groups had a 1.33-fold and 1.34-fold elevated risk of new-onset cardiovascular events, respectively. These trends were consistent across cardiovascular event subtypes. Conclusions Nonadherence to antihypertensive medication was common in patients with cancer and was associated with worse clinical outcomes in adult patients with cancer with hypertension. More attention should be paid to improving adherence to antihypertensive medication among patients with cancer.

Trans-Aortic Flow Turbulence and Aortic Valve Inflammation: A Pilot Study Using Blood Speckle Imaging and 18F-Sodium Fluoride Positron Emission Tomography/Computed Tomography in Patients With Moderate Aortic Stenosis.

BACKGROUND: 18F-sodium fluoride positron emission tomography/computed tomography (18F-NaF PET/CT) has been proven to be useful in identification of microcalcifications, which are stimulated by inflammation. Blood speckle imaging (BSI) is a new imaging technology used for tracking the flow of blood cells using transesophageal echocardiography (TEE). We evaluated the relationship between turbulent flow identified by BSI and inflammatory activity of the aortic valve (AV) as indicated by the 18F-NaF uptake index in moderate aortic stenosis (AS) patients. METHODS: This study enrolled 18 moderate AS patients diagnosed within the past 6 months. BSI within the aortic root was acquired using long-axis view TEE. The duration of laminar flow and the turbulent flow area ratio were calculated by BSI to demonstrate the degree of turbulence. The maximum and mean standardized uptake values (SUVmax, SUVmean) and the total microcalcification burden (TMB) as measured by 18F-NaF PET/CT were used to demonstrate the degree of inflammatory activity in the AV region. RESULTS: The mean SUVmean, SUVmax, and TMB were 1.90 ± 0.79, 2.60 ± 0.98, and 4.20 ± 2.18 mL, respectively. The mean laminar flow period and the turbulent area ratio were 116.1 ± 61.5 msec and 0.48 ± 0.32. The correlation between SUVmax and turbulent flow area ratio showed the most positive and statistically significant correlation, with a Pearson's correlation coefficient (R²) of 0.658 and a p-value of 0.014. CONCLUSIONS: The high degree of trans-aortic turbulence measured by BSI was correlated with severe AV inflammation.

Review of North Korean Reports on Cardiovascular Disease Research and Management.

PURPOSE: This study aimed to investigate the quality of medical care in North Korea using data from North Korean medical research. MATERIALS AND METHODS: This study included publications containing the keyword "medical" among North Korea's consecutive publications and selected 415 papers related to heart disease, brain disease, and emergency medical care published at The North Korean Data Center of the Ministry of Unification (https://unibook.unikorea.go.kr). Among 40 research articles, we reviewed ten with representative epidemiological data for cardiovascular treatment, and the latest medical materials were selected and analyzed in detail. RESULTS: Few studies reported the experience of large-scale medical facilities or verified professional performance. Proof of the efficacy of the latest drugs was rare, although the treatment results of interventional therapy and conventional heart surgery were reported. Efforts to improve emergency medical care and innovation of treatment materials using new technologies were being actively studied. However, careful interpretation is required due to the lack of objectivity in research data and some deviation in the composition of patients included in the data. CONCLUSION: Research of cardiovascular disease in North Korea is conducted at a very limited scope, although treatment results appear to be recorded. The management of cardiovascular disease and the establishment of an emergency medical system warrant global attention and cooperation for further improvement.

Central hemodynamics and the discrepancy between central blood pressure and brachial blood pressure.

Despite similar brachial blood pressure, central hemodynamics could be different. The objective of the present study was to investigate the factors, which could influence the discrepancy between central BP (cBP) and brachial blood pressure. Six hundred forty-seven patients (364 males, 48 ± 12 years old) were enrolled. Using applanation tonometry, cBP was noninvasively derived. The median difference between brachial systolic BP (bSBP) and central systolic BP (cSBP) was 8 mm Hg. We defined the discrepancy between bSBP and cSBP as differences >8 mm Hg. For adjustment of cBP, population was divided into 3 groups according to the cBP: group 1, <140 mm Hg of cSBP; group 2, 140 > cSBP < 160 mm Hg; group 3, =160 mm Hg of cSBP. All the central hemodynamic parameters of the patients, including augmentation pressure, augmentation index (AI), heart rate (75 bpm) adjusted augmentation index (AI@HR75), and subendocardial viability ratio, were measured. Using multivariate logistic regression analysis, we evaluated the factors which could influence the discrepancy between bSBP and cSBP. Age, gender, augmentation pressure, AI, and AI@HR75 were correlated with the discrepancy between bSBP and cSBP. AI@HR75 was significantly correlated with the discrepancy between bSBP and cSBP (ß-coefficient = -0.376, P < .001 in group 1; ß-coefficient = -0.297, P < .001 in group 2; and ß-coefficient = -0.545, P < .001 in group 3). In groups 1 and 2, male gender was significantly correlated with the discrepancy between bSBP and cSBP (ß-coefficient = -0.857, P = .035 in group 1; ß-coefficient = -1.422, P = .039 in group 2). In present study, arterial stiffness might affect the discrepancy between bSBP and cSBP. Also, male gender was closely related to the discrepancy between bSBP and cSBP especially with cSBP <160 mm Hg. Not only cSBP, the discrepancy between cSBP and bSBP should be considered for understanding the central hemodynamics.

Clinical impact of statin intensity according to age in patients with acute myocardial infarction.

BACKGROUND: The available data are not sufficient to understand the clinical impact of statin intensity in elderly patients who undergo percutaneous coronary intervention (PCI) due to acute myocardial infarction (AMI). METHODS: Using the COREA-AMI registry, we sought to compare the clinical impact of high- versus low-to-moderate-intensity statin in younger (<75 years old) and elderly (≥75 years old) patients. Of 10,719 patients, we included 8,096 patients treated with drug-eluting stents. All patients were classified into high-intensity versus low-to-moderate-intensity statin group according to statin type and dose at discharge. The primary end point was target-vessel failure (TVF), a composite of cardiovascular death, target-vessel MI, or target-lesion revascularization (TLR) from 1 month to 12 months after index PCI. RESULTS: In younger patients, high-intensity statin showed the better clinical outcomes than low-to-moderate-intensity statin (TVF: 79 [5.4%] vs. 329 [6.8%], adjusted hazard ratio [aHR] 0.76; 95% confidence interval [CI] 0.59-0.99; P = 0.038). However, in elderly patients, the incidence rates of the adverse clinical outcomes were similar between two statin-intensity groups (TVF: 38 [11.4%] vs. 131 [10.6%], aHR 1.1; 95% CI 0.76-1.59; P = 0.63). CONCLUSIONS: In this AMI cohort underwent PCI, high-intensity statin showed the better 1-year clinical outcomes than low-to-moderate-intensity statin in younger patients. Meanwhile, the incidence rates of adverse clinical events between high- and low-to-moderate-intensity statin were not statistically different in elderly patients. Further randomized study with large elderly population is warranted.

Associations between the triglyceride-glucose index and cardiovascular disease in over 150,000 cancer survivors: a population-based cohort study.

BACKGROUND: The prevention of subsequent cardiovascular disease (CVD) is an essential part of cancer survivorship care. We conducted the present study to investigate the association between the TyG index (a surrogate marker of insulin resistance) and the risk of cardiovascular disease (CVD) events in cancer survivors. METHODS: Adult cancer patients, who underwent routine health examinations during 2009-2010 and were survived for more than 5 years as of January 1, 2011, were followed for hospitalization of CVD (either ischemic heart disease, stroke, or heart failure) until December 2020. Cox model was used to calculate hazard ratios associated with baseline TyG index (loge [fasting triglyceride (mg) × fasting glucose (mg)/2]) for the CVD hospitalization. RESULTS: A total of 155,167 cancer survivors (mean age 59.9 ± 12.0 years, female 59.1%) were included in this study. A graded positive association was observed between TyG and CVD hospitalization. An 8% elevated risk for CVD hospitalization was observed for a TyG index of 8-8.4 (aHR 1.08 [95% CI 1.01-1.14]); 10% elevated risk for a TyG index of 8.5-8.9 (aHR 1.10 [95% CI 1.03-1.17]); 23% elevated risk for a TyG index of 9.0-9.4 (aHR 1.23 [95% CI 1.15-1.31]); 34% elevated risk for a TyG index of 9.5-9.9 (aHR 1.34 [95% CI 1.23-1.47]); and 55% elevated risk for a TyG index ≥ 10 compared to the reference group (TyG index < 8). Per 1-unit increase in the TyG index, a 16% increase in CVD hospitalization and a 45% increase in acute myocardial infarction hospitalization were demonstrated. Graded positive associations were evident for atherosclerotic CVD subtypes, such as ischemic heart disease, acute myocardial infarction, and ischemic stroke, but not for hemorrhagic stroke or heart failure. CONCLUSIONS: The TyG index may serve as a simple surrogate marker for the risk stratification of future CVD events, particularly atherosclerotic subtypes, in cancer survivors.

Long-Term Maintenance of Sinus Rhythm Is Associated with Favorable Echocardiographic Remodeling and Improved Clinical Outcomes after Transcatheter Aortic Valve Replacement.

Periprocedural atrial fibrillation (AF) is associated with poor prognosis after transcatheter aortic valve replacement (TAVR). We evaluated the impact of long-term sinus rhythm (SR) maintenance on post-TAVR outcomes. We enrolled 278 patients treated with TAVR including 87 patients with periprocedural AF. Patients with periprocedural AF were classified into the AF-sinus rhythm maintained (AF-SRM) group or the sustained AF group according to long-term cardiac rhythm status after discharge. Patients without AF before or after TAVR were classified into the SR group. The primary clinical outcome was a composite of all-cause death, stroke, or heart failure rehospitalization. The AF-SRM and the SR groups showed significant improvements in left ventricular ejection fraction and left atrial volume index at one year after TAVR, while the sustained AF group did not. During 24.5 (±16.1) months of follow-up, the sustained AF group had a higher risk of the adverse clinical event compared with the AF-SRM group (hazard ratio (HR) 4.449, 95% confidence interval (CI) 1.614-12.270), while the AF-SRM group had a similar risk of the adverse clinical event compared with the SR group (HR 0.737, 95% CI 0.285-1.903). In conclusion, SR maintenance after TAVR was associated with enhanced echocardiographic improvement and favorable clinical outcomes.

Temporal Trends of Major Bleeding and Its Prediction by the Academic Research Consortium-High Bleeding Risk Criteria in Acute Myocardial Infarction.

Limited data exist on the temporal trend of major bleeding and its prediction by the Academic Research Consortium-High Bleeding Risk (ARC-HBR) criteria in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI). We investigated 10-year trends of major bleeding and predictive ability of the ARC-HBR criteria in AMI patients. In a multicenter registry of 10,291 AMI patients undergoing PCI between 2004 and 2014 the incidence of Bleeding Academic Research Consortium (BARC) 3 and 5 bleeding was assessed, and, outcomes in ARC-defined HBR patients with AMI were compared with those in non-HBR. The primary outcome was BARC 3 and 5 bleeding at 1 year. Secondary outcomes included all-cause mortality and composite of cardiovascular death, myocardial infarction, or ischemic stroke. The annual incidence of BARC 3 and 5 bleeding in the AMI population has increased over the years (1.8% to 5.8%; p < 0.001). At 1 year, ARC-defined HBR (n = 3371, 32.8%) had significantly higher incidence of BARC 3 and 5 bleeding (9.8% vs. 2.9%; p < 0.001), all-cause mortality (22.8% vs. 4.3%; p < 0.001) and composite of ischemic events (22.6% vs. 5.8%; p < 0.001) compared to non-HBR. During the past decade, the incidence of major bleeding in the AMI population has increased. The ARC-HBR criteria provided reliable predictions for major bleeding, mortality, and ischemic events in AMI patients.

Association of Physical Activity and Lower Respiratory Tract Infection Outcomes in Patients With Cardiovascular Disease.

Background To investigate the dose-response association between physical activity and lower respiratory tract infection (LoRI) outcomes in patients with cardiovascular disease. Methods and Results Using the Korean National Health Insurance data, we identified individuals aged 18 to 99 years (mean age, 62.6±11.3 years; women, 49.6%) with cardiovascular disease who participated in health screening from January 1, 2009, to December 31, 2012 (n=1 048 502), and were followed up until 2018 for mortality and until 2019 for hospitalization. Amount of physical activity was assessed using self-reported questionnaires and categorized into 5 groups: 0 (completely sedentary), <500, 500 to 999, 1000 to 1499, and ≥1500 metabolic equivalents of task min/wk. After controlling for various confounders, adjusted hazard ratios (95% CIs) were 1.00 (reference), 0.74 (0.70-0.78), 0.66 (0.62-0.70), 0.52 (0.47-0.57), and 0.54 (0.49-0.60) for LoRI mortality, and 1.00 (reference), 0.84 (0.83-0.85), 0.77 (0.76-0.79), 0.72 (0.70-0.73), and 0.71 (0.69-0.73) for LoRI hospitalization among those engaging in physical activity of 0, <500, 500 to 999, 1000 to 1499, and ≥1500 metabolic equivalents of task min/wk, respectively. Assuming linear association between 0 and 2000 metabolic equivalents of task min/wk, each 500-metabolic equivalents of task min/wk increase of physical activity was associated with reduced LoRI mortality and hospitalization by 22% and 13%, respectively. The negative association was stronger in the older population than in the younger population (P for interaction <0.01). Conclusions In patients with cardiovascular disease, engaging in even a low level of physical activity was associated with a decreased risk of mortality and hospitalization from LoRI than being completely sedentary, and incremental risk reduction was observed with increased physical activity.

A Prospective Randomized, Double-Blind, Multi-Center, Phase III Clinical Trial Evaluating the Efficacy and Safety of Olmesartan/Amlodipine plus Rosuvastatin Combination Treatment in Patients with Concomitant Hypertension and Dyslipidemia: A LEISURE Study.

BACKGROUND: This study was a multicenter, randomized, double-blinded, placebo-controlled phase III clinical trial to investigate the efficacy and safety of an olmesartan/amlodipine single pill plus rosuvastatin combination treatment for patients with concomitant hypertension and dyslipidemia. METHODS: Patients with both hypertension and dyslipidemia aged 20-80 were enrolled from 36 tertiary hospitals in Korea from January 2017 to April 2018. Patients were randomized to three groups in a 1:1:0.5 ratio, olmesartan/amlodipine single pill plus rosuvastatin (olme/amlo/rosu) or olmesartan plus rosuvastatin (olme/rosu) or olmesartan/amlodipine single pill (olme/amlo) combination. The primary endpoints were change of sitting systolic blood pressure (sitSBP) from baseline in the olme/amlo/rosu vs. olme/rosu groups and the percentage change of low-density lipoprotein cholesterol (LDL-C) from baseline in the olme/amlo/rosu vs. olme/amlo groups after 8 weeks of treatment. RESULTS: A total of 265 patients were randomized, 106 to olme/amlo/rosu, 106 to olme/rosu and 53 to olme/amlo groups. Baseline characteristics among the three groups did not differ. The mean sitSBP change was significantly larger in the olme/amlo/rosu group with -24.30 ± 12.62 mmHg (from 153.58 ± 10.90 to 129.28 ± 13.58) as compared to the olme/rosu group, -9.72 ± 16.27 mmHg (from 153.71 ± 11.10 to 144.00 ± 18.44 mmHg). The difference in change of sitSBP between the two groups was -14.62± 1.98 mmHg with significance (95% CI -18.51 to -10.73, p < 0.0001). The mean LDL-C reduced significantly in the olme/amlo/rosu group, -52.31 ± 16.63% (from 154.52 ± 30.84 to 72.72 ± 26.08 mg/dL) as compared to the olme/amlo group with no change, -2.98 ± 16.16% (from 160.42 ± 32.05 to 153.81 ± 31.57 mg/dL). Significant difference in change was found in LDL-C between the two groups with -50.10 ± 2.73% (95% CI -55.49 to -44.71, p < 0.0001). Total adverse drug reaction rates were 10.48%, 5.66% and 3.7% in the olme/amlo/rosu, olme/rosu and olme/amlo groups, respectively with no statistical significance among the three groups. Serious adverse drug reactions did not occur. CONCLUSIONS: Olmesartan/amlodipine single pill plus rosuvastatin combination treatment for patients with both hypertension and dyslipidemia is effective and safe as compared to either olmesartan plus rosuvastatin or olmesartan plus amlodipine treatment.

Visit-to-visit blood pressure variability and mortality and cardiovascular outcomes after acute myocardial infarction.

The relationship between visit-to-visit blood pressure variability (BPV) and cardiovascular outcomes remains unclear. Our study assessed the prognostic implications of visit-to-visit BPV in patients after acute myocardial infarction (AMI). The present study enrolled 7,375 patients who underwent percutaneous coronary intervention for AMI and at least five measurements of blood pressure after hospital discharge. Visit-to-visit BPV was estimated as variability independent of mean. The primary endpoint was all-cause mortality. The secondary endpoints were major cardiovascular events (the composite of cardiovascular death, myocardial infarction, and ischemic stroke) and hospitalization for heart failure. During a median follow-up of 5.8 years, adjusted risks of all-cause mortality, major cardiovascular events, and hospitalization for heart failure continuously increased as systolic BPV and diastolic BPV increased. Patients in the highest quartile of systolic BPV (versus lowest) had increased risk of all-cause mortality (adjusted hazard ratio (aHR) 1.51 [95% confidence interval (CI) 1.23-1.85]), major cardiovascular events (aHR 1.31 [95% CI 1.1-1.55]), and hospitalization for heart failure (aHR 2.15 [95% CI 1.49-3.1]). Patients in the highest quartile of diastolic BPV was also associated with all-cause mortality (aHR 1.39 [95% CI 1.14-1.7]), major cardiovascular events (aHR 1.29 [95% CI 1.08-1.53]), and hospitalization for heart failure (aHR 2.01[95% CI 1.4-2.87]). Both systolic and diastolic BPV improved the predictive ability of the GRACE (Global Registry of Acute Coronary Events) risk score for both all-cause mortality and major cardiovascular events. Higher visit-to-visit BPV was associated with increased risks of mortality and cardiovascular events in patients after AMI.

Impact of Intravascular Ultrasound on Long-Term Clinical Outcomes in Patients With Acute Myocardial Infarction.

OBJECTIVES: The aim of this study was to examine the impact of intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) on long-term clinical outcomes in patients with acute myocardial infarction (AMI). BACKGROUND: IVUS-guided PCI has been associated with improved cardiovascular outcomes. However, the beneficial effect of IVUS-guided PCI in patients with AMI in the drug-eluting stent era remains unclear. METHODS: Patients who underwent PCI with drug-eluting stents were selected from 10,719 patients enrolled in a multicenter AMI registry. The included patients were classified into 2 groups according to the use or nonuse of IVUS. The primary outcome was a composite of major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and target lesion revascularization, during long-term follow-up. RESULTS: A total of 9,846 patients were treated with IVUS-guided PCI (n = 2,032) or angiography-guided PCI (n = 7,814). IVUS-guided PCI was associated with reduced MACE (HR: 0.779; 95% CI: 0.689-0.880; P < 0.001). The results were consistent after multivariable regression and propensity score matching. One-year landmark analysis showed a lower risk for MACE within 1 year (HR: 0.766; 95% CI: 0650-0.903; P = 0.002) and beyond 1 year (HR: 0.796; 95% CI: 0663-0.956; P = 0.014) after index PCI. CONCLUSIONS: The use of IVUS was associated with better long-term cardiovascular outcomes. The clinical benefit of IVUS was maintained both within and beyond 1 year after index PCI. The use of IVUS in PCI should be considered for patients with AMI.

A Standardized Lindera obtusiloba Extract Improves Endothelial Dysfunction and Attenuates Plaque Development in Hyperlipidemic ApoE-Knockout Mice.

Lindera obtusiloba extract (LOE), a traditional herbal medicine used to enhance blood circulation and to reduce inflammation, induced NO-mediated endothelium-dependent relaxation, and reduced the formation of reactive oxygen species (ROS). The study investigated whether LOE improves endothelial dysfunction and reduces plaque inflammation and progression by inhibiting ROS generation in a mouse model of atherosclerosis. Eight-week-old apolipoprotein E-deficient (apoE-/-) mice fed with a western diet (WD) were randomized into different groups by administering vehicle (0.5% carboxymethylcellulose (CMC)), LOE (100 mg/kg/day), or losartan (30 mg/kg/day) by gavage until the age of 28 weeks. Fourteen male C57BL/6 mice that were fed normal chow and treated with CMC were used as negative controls. Similar to losartan treatment, LOE treatment induced the concentration-dependent relaxation of aorta rings in WD-fed apoE-/- mice. LOE treatment significantly reduced the vascular ROS formation and expression of NADPH oxidase subunits, including p22phox and p47phox. Compared with WD-fed apoE-/- mice, mice exposed to chronic LOE treatment exhibited reductions in plaque inflammation-related fluorescence signals and atherosclerotic lesions. These effects were greater than those of losartan treatment. In conclusion, LOE treatment improves endothelial dysfunction and reduces plaque inflammation as well as lesion areas by reducing vascular NADPH oxidase-induced ROS generation in a mouse model of atherosclerosis.

Comparison of the Efficacy and Safety of Atorvastatin 40 mg/ω-3 Fatty Acids 4 g Fixed-dose Combination and Atorvastatin 40 mg Monotherapy in Hypertriglyceridemic Patients who Poorly Respond to Atorvastatin 40 mg Monotherapy: An 8-week, Multicenter, Randomized, Double-blind Phase III Study.

PURPOSE: Residual cardiovascular risk in patients with hypertriglyceridemia, despite optimal low-density lipoprotein cholesterol levels being achieved with intensive statin treatment, is a global health issue. The purpose of this study was to investigate the efficacy and tolerability of treatment with a combination of high-dose atorvastatin/Ω-3 fatty acid compared to atorvastatin + placebo in patients with hypertriglyceridemia who did not respond to statin treatment. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study, patients who had residual hypertriglyceridemia after a 4-week run-in period of atorvastatin treatment were randomly assigned to receive UI-018 (fixed-dose combination atorvastatin/Ω-3 fatty acid 40 mg/4 g) or atorvastatin 40 mg + placebo (control). The primary efficacy end points were the percentage change from baseline in non-high density lipoprotein cholesterol (non-HDL-C) level at the end of treatment and the adverse events recorded during treatment. A secondary end point was the percentage change from baseline in triglyceride level. FINDINGS: After 8 weeks of treatment, the percentage changes from baseline in non-HDL-C (-4.4% vs +0.6%; p = 0.02) and triglycerides (-18.5% vs +0.9%; p < 0.01) were significantly greater in the UI-018 group (n = 101) than in the control group (n = 99). These changes were present in subgroups of advanced age (≥65 years), status (body mass index ≥25 kg/m2), or without diabetes. The prevalences of adverse events did not differ between the 2 treatment groups. IMPLICATIONS: In patients with residual hypertriglyceridemia despite receiving statin treatment, a combination of high-dose atorvastatin/Ω-3 fatty acid was associated with a greater reduction of triglyceride and non-HDL-C compared with atorvastatin + placebo, without significant adverse events.

Risks of Recurrent Cardiovascular Events and Mortality in 1-Year Survivors of Acute Myocardial Infarction Implanted with Newer-Generation Drug-Eluting Stents.

Current treatments for acute myocardial infarction (AMI) have dramatically improved clinical outcomes during the first year after AMI. Less is known, however, about the subsequent risks of recurrent cardiovascular events and mortality in patients who survive 1 year after AMI. The purpose of the present study is to evaluate long-term clinical outcomes in 1-year AMI survivors who were implanted with newer-generation drug-eluting stents (DESs) since 2010. The COREA-AMI (CardiOvascular Risk and idEntificAtion of potential high-risk population in AMI) registry consecutively enrolled AMI patients who underwent percutaneous coronary intervention (PCI), and patients who received newer-generation DESs since 2010 were analyzed. The primary endpoint was major adverse cardiovascular events (MACEs), and secondary endpoint was all-cause mortality. Of 6242 AMI patients, 5397 were alive 1 year after the index procedure. The cumulative incidence of MACEs and all-cause death 1 to 7 years after AMI were 28.4% (annually 4-6%) and 20.2% (annually 3-4%), respectively. Multivariate analysis showed that uncontrolled systolic blood pressure (SBP) and serum low-density lipoprotein cholesterol (LDL-C) concentration, as well as traditional risk factors, were associated with MACEs and all-cause death. Recurrent non-fatal myocardial infarction, ischemic stroke, and bleeding events within 1 year were significantly associated with all-cause death. The risks of adverse cardiovascular events and death remain high in AMI patients more than 1 year after the index PCI with newer-generation DESs. Traditional risk factors, uncontrolled SBP and LDL-C, and non-fatal adverse events within 1 year after the index procedure strongly influence long-term clinical outcomes.

Activation of Aryl Hydrocarbon Receptor by ITE Improves Cardiac Function in Mice After Myocardial Infarction.

Background The immune and inflammatory responses play a considerable role in left ventricular remodeling after myocardial infarction (MI). Binding of AhR (aryl hydrocarbon receptor) to its ligands modulates immune and inflammatory responses; however, the effects of AhR in the context of MI are unknown. Therefore, we evaluated the potential association between AhR and MI by treating mice with a nontoxic endogenous AhR ligand, ITE (2-[1'H-indole-3'-carbonyl]-thiazole-4-carboxylic acid methyl ester). We hypothesized that activation of AhR by ITE in MI mice would boost regulatory T-cell differentiation, modulate macrophage activity, and facilitate infarct healing. Methods and Results Acute MI was induced in C57BL/6 mice by ligation of the left anterior descending coronary artery. Then, the mice were randomized to daily intraperitoneal injection of ITE (200 µg/mouse, n=19) or vehicle (n=16) to examine the therapeutic effects of ITE during the postinfarct healing process. Echocardiographic and histopathological analyses revealed that ITE-treated mice exhibited significantly improved systolic function (P<0.001) and reduced infarct size compared with control mice (P<0.001). In addition, we found that ITE increased regulatory T cells in the mediastinal lymph node, spleen, and infarcted myocardium, and shifted the M1/M2 macrophage balance toward the M2 phenotype in vivo, which plays vital roles in the induction and resolution of inflammation after acute MI. In vitro, ITE expanded the Foxp3+ (forkhead box protein P3-positive) regulatory T cells and tolerogenic dendritic cell populations. Conclusions Activation of AhR by a nontoxic endogenous ligand, ITE, improves cardiac function after MI. Post-MI mice treated with ITE have a significantly lower risk of developing advanced left ventricular systolic dysfunction than nontreated mice. Thus, the results imply that ITE has a potential as a stimulator of cardiac repair after MI to prevent heart failure.

Candesartan and carvedilol for primary prevention of subclinical cardiotoxicity in breast cancer patients without a cardiovascular risk treated with doxorubicin.

BACKGROUND: There is no proven primary preventive strategy for doxorubicin-induced subclinical cardiotoxicity (DISC), especially among patients without a cardiovascular (CV) risk. We investigated the primary preventive effect on DISC of the concomitant use of angiotensin receptor blockers (ARBs) or beta-blockers (BBs), especially among breast cancer patients without a CV risk. METHODS: A total of 385 patients who were scheduled for doxorubicin chemotherapy were screened. Among them, 195 patients of the study populations were included and were randomly divided into two groups [candesartan 4 mg q.d. vs. carvedilol 3.125 mg q.d.] and patients who were unwilling to take one of the medications were evaluated as controls. The primary outcomes were the incidence of early DISC (DISC developing within 6 months after chemotherapy), and late DISC (DISC developing only at least 12 months after chemotherapy). RESULT: Compared with the control group (8 out of 43 patients (18.6%)), only the candesartan group (4 out of 82 patients (4.9%)) showed a significantly lower incidence of early DISC (p = 0.022). Compared with the control group, the candesartan group demonstrated a significantly reduced decrease in left ventricular ejection fraction (LVEF) throughout the study period [-1.0% vs. -3.00 (p < 0.001) at the first follow-up, -1.10% vs. -3.40(p = 0.009) at the second follow-up]. CONCLUSIONS: Among breast cancer patients without a CV risk treated with doxorubicin-containing chemotherapy, subclinical cardiotoxicity is prevalent and concomitant administration of low-dose candesartan might be effective to prevent an early decrease in LVEF. Further large-scale, randomized controlled trials will be needed to confirm our findings.

Effects of Smoking on Long-Term Clinical Outcomes and Lung Cancer in Patients with Acute Myocardial Infarction.

BACKGROUND AND OBJECTIVES: Smoking is well-established as a risk factor for coronary artery disease. However, recent studies demonstrated favorable results, including reduced mortality, among smokers, which are referred to as the "smoker's paradox". This study examined the impact of smoking on clinical outcomes in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). METHODS: Patients with AMI undergoing PCI between 2004 and 2014 were enrolled and classified according to smoking status. The primary endpoint was a composite of major adverse cardiovascular events (MACE) including cardiac death, myocardial infarction, stroke, and revascularization. RESULTS: Among the 10,683 patients, 4,352 (40.7%) were current smokers. Smokers were 10.7 years younger and less likely to have comorbidities such as hypertension, diabetes mellitus, chronic kidney disease, stroke, and prior PCI. Smokers had less MACE (hazard ratio [HR], 0.644; 95% confidence interval [CI], 0.594-0.698; p<0.001) and cardiac death (HR, 0.494; 95% CI, 0.443-0.551; p<0.001) compared to nonsmokers during the 5 years in an unadjusted model. However, after propensity-score matching, smokers showed higher risk of MACE (HR, 1.125; 95% CI, 1.009-1.254; p=0.034) and cardiac death (HR, 1.190; 95% CI, 1.026-1.381; p=0.022). Smoking was a strong independent predictor of lung cancer (propensity-score matched HR, 2.749; 95% CI, 1.416-5.338; p=0.003). CONCLUSIONS: In contrast to the unadjusted model, smoking is associated with worse cardiovascular outcome and higher incidence of lung cancer after adjustment of various confounding factors. This result can be explained by the characteristics of smokers, which were young and had fewer comorbidities.